Leslie John B, Gan Tong J
College of Medicine, Mayo Clinic, Mayo Clinic Hospital, Mayo Clinic Arizona, Scottsdale, AZ 85259-5404, USA.
Ann Pharmacother. 2006 May;40(5):856-72. doi: 10.1345/aph.1G381. Epub 2006 May 2.
Antiemetic guidelines recommend a combination of serotonin (5-HT3) with a second agent such as droperidol or dexamethasone. Physicians have been reluctant to employ these guidelines due to concerns over the black-box warning of droperidol and safety concerns with a steroid.
To assess the safety profiles of 5-HT3 receptor antagonist (5-HT3RA) monotherapy and combination therapy with a steroid or droperidol for prophylaxis of postoperative nausea and vomiting (PONV).
A MEDLINE search of English-language reports of randomized controlled trials (RCTs) was conducted (1966-September 2005) using the key terms 5-HT3, granisetron, ondansetron, dolasetron, tropisetron, PONV, postoperative, vomiting, emesis, and nausea. RCTs with treatment arms comparing 5-HT3RA monotherapy (granisetron, ondansetron, dolasetron, or tropisetron) with dexamethasone or droperidol or 5-HT3RA combinations and providing incidence data on adverse events were identified and reviewed. Within-study odds ratios with 95% confidence intervals were calculated to determine the incidence rates of all adverse events in RCTs using 5-HT3RA monotherapy and combination therapies. Overall effect sizes for frequently reported adverse events were estimated by pooling ORs using fixed- and random-effect models.
Pooled ORs (OR(pooled)) for adverse events with 5-HT3RA/dexamethasone versus 5-HT3RA for PONV prophylaxis were not significant for any reported adverse events or the overall incidence of adverse events; 5-HT3RA/droperidol versus 5-HT3RA was significant only for decreased headache incidence (fixed model: OR(pooled) 0.35; 95% CI 0.18 to 0.69). The OR(pooled) for 5-HT3RA/dexamethasone versus dexamethasone was not significant for any reported adverse events except headaches (fixed model OR(pooled) 1.75; 95% CI 1.01 to 3.03), none of which was serious. OR(pooled) for 5-HT3RA/droperidol versus droperidol was not significant for any reported adverse events. Avascular necrosis, occult infection, and delayed wound healing were not observed with either combination therapy. Cardiac abnormalities were observed with 5-HT3RA/droperidol therapy.
This meta-analysis indicates that either therapy has a safety profile similar to that of dexamethasone, droperidol, or 5-HT3RA.
止吐指南推荐将5-羟色胺（5-HT3）与第二种药物（如氟哌利多或地塞米松）联合使用。由于对氟哌利多的黑框警告以及类固醇药物的安全性担忧，医生一直不愿采用这些指南。
评估5-羟色胺3型受体拮抗剂（5-HT3RA）单药治疗以及与类固醇或氟哌利多联合治疗预防术后恶心和呕吐（PONV）的安全性。
利用关键词5-HT3、格拉司琼、昂丹司琼、多拉司琼、托烷司琼、PONV、术后、呕吐、反胃和恶心，对1966年至2005年9月期间MEDLINE收录的英文随机对照试验（RCT）报告进行检索。纳入并分析了比较5-HT3RA单药治疗（格拉司琼、昂丹司琼、多拉司琼或托烷司琼）与地塞米松或氟哌利多或5-HT3RA联合治疗且提供不良事件发生率数据的RCT治疗组。计算研究内比值比及95%置信区间，以确定使用5-HT3RA单药治疗和联合治疗的RCT中所有不良事件的发生率。通过固定效应模型和随机效应模型合并比值比，估计常见不良事件的总体效应大小。
对于预防PONV，5-HT3RA/地塞米松与5-HT3RA相比，任何报告的不良事件或不良事件总体发生率的合并比值比均无统计学意义；5-HT3RA/氟哌利多与5-HT3RA相比，仅头痛发生率降低有统计学意义（固定模型：合并比值比0.35；95%置信区间0.18至0.69）。5-HT3RA/地塞米松与地塞米松相比，除头痛外（固定模型合并比值比1.75；95%置信区间1.01至3.03），任何报告的不良事件的合并比值比均无统计学意义，且均不严重。5-HT3RA/氟哌利多与氟哌利多相比，任何报告的不良事件的合并比值比均无统计学意义。两种联合治疗均未观察到缺血性坏死、隐匿性感染和伤口愈合延迟。5-HT3RA/氟哌利多治疗观察到心脏异常。
这项荟萃分析表明，两种治疗方法的安全性与地塞米松、氟哌利多或5-HT3RA相似。
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